Vascular smooth muscle-derived tissue factor is critical for arterial thrombosis after ferric chloride-induced injury.
Tissue factor (TF) initiates coagulation, regulates hemostasis, and plays a critical role in mediating arterial thrombosis. TF is up-regulated in vascular smooth muscle cells (VSMCs) in atherosclerosis and arterial injury. To examine the biologic role of VSMC-derived TF, we crossed TF(flox/flox) mice with SM22alphaCre(+/-) mice. TF mRNA and activity were decreased in the aortic media of TF-deficient mice by 96% and 94.8%, respectively. There were no differences in TF activity measured in plasma or concentrated microparticles. TF-deficient mice were generated with the expected frequency, showed no evidence of bleeding or increased mortality, and had similar activated partial thromboplastin and tail vein bleeding times. Thrombus-mediated flow reduction in response to ferric chloride injury of the carotid arteries was significantly attenuated in VSMC-specific TF-deficient. Stable occlusion was seen in 11 of 12 wild-type mice, but in only 6 of 16 VSMC-specific TF-deficient mice (P = .001). These data suggest that VSMC-derived TF is critical in a macrovascular model of arterial thrombosis. This mouse model should be valuable in determining the contribution of VSMC-derived TF in other TF-mediated phenomena, such as restenosis.
Wang
Li
L
Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester, NY, USA.
Miller
Christine
C
Swarthout
Robert F
RF
Rao
Mohan
M
Mackman
Nigel
N
Taubman
Mark B
MB
D000818:Animals; D001011:Aorta / Q000473:pathology; D002341:Carotid Artery Thrombosis / Q000378:metabolism* / Q000473:pathology; D002712:Chlorides; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005290:Ferric Compounds / Q000633:toxicity*; D005355:Fibrosis; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009206:Myocardium / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009676:Noxae / Q000633:toxicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D013927:Thrombosis / Q000473:pathology
D002712:Chlorides; D005290:Ferric Compounds; D009676:Noxae; D013925:Thromboplastin; C024555:ferric chloride